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Utility of 18F-Fluorodeoxyglucose Positron Emission
Tomography in Inflammatory Rheumatism, Particularly
Polymyalgia Rheumatica: A Retrospective Study of 222
PET/CT
Julie Amat, Marion Chanchou, Louis Olagne, Lucie Descamps, Anthime
Flaus, Clément Bouvet, Bertrand Barres, Clémence Valla, Ioana Molnar,
Arnaud Cougoul, et al.
To cite this version:
Julie Amat, Marion Chanchou, Louis Olagne, Lucie Descamps, Anthime Flaus, et al.. Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography in Inflammatory Rheumatism, Particularly Polymyalgia Rheumatica: A Retrospective Study of 222 PET/CT. Frontiers in Medicine, Frontiers media, 2020, 7, �10.3389/fmed.2020.00394�. �hal-03028990�
1
Utility of
18F-fluorodeoxyglucose positron emission tomography in
inflammatory rheumatism, particularly polymyalgia rheumatica:
a retrospective study of 222 PET/CT
Authors : Julie AMAT1, Marion CHANCHOU1, Louis OLAGNE2, Lucie DESCAMPS3, Anthime FLAUS4, Clément BOUVET1, Bertrand BARRES1, Clemence VALLA1, Ioana MOLNAR5, Arnaud COUGOUL5, Sylvain MATHIEU3, Olivier AUMAITRE2, Martin SOUBRIER3, Antony KELLY1, Charles MERLIN1, Florent CACHIN1
1
Jean Perrin Oncology Institute, Department of Nuclear Medicine, Clermont-Ferrand, France.
2
Gabriel Montpied University Hospital, Department of Internal Medicine University of Clermont-Ferrand, France.
3
Gabriel Montpied University Hospital, Department of rheumatology University of Clermont-Ferrand, France.
4
North University Hospital, Department of Nuclear Medicine, University of Saint-Etienne, France.
5
Jean Perrin Oncology Institute, Department of Biostatistics Clermont-Ferrand, France.
Julie AMAT, 58 rue Montalembert, 63011 Clermont-Ferrand, France, Téléphone : 0473278081, Fax : 0473278078, julie.amat@clermont.unicancer.fr, first author.
*Florent CACHIN, 58 rue Montalembert, 63011 Clermont-Ferrand, France, Téléphone : 0473278081, Fax : 0473278078, florent.cachin@clermont.unicancer.fr, corresponding author.
6239 words, 3 figures
2 Utility of 18F-fluorodeoxyglucose positron emission tomography in inflammatory rheumatism, particularly polymyalgia rheumatica: a retrospective study of 222 PET/CT
Summary
Purpose: The objective of this study was to evaluate periarticular FDG uptake scores from 18F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population
presenting rheumatic diseases.
Methods: A French retrospective study from 2011 to 2015 was conducted. Patients who
underwent 18F-FDG-PET/CT for diagnosis or follow-up of a rheumatism or an unexplained
biological inflammatory syndrome were included. Clinical data and final diagnosis were
reviewed.
Seventeen periarticular sites were sorted by a visual reading enabling us to calculate two
scores: mean FDG visual uptake score, number of sites with significant uptake same or higher
than liver uptake intensity and by a semi-quantitative analysis using mean maximum
standardized uptake value (SUVmax). Optimal cut-offs of visual score and SUVmax to
diagnose PMR were determined using receiver operating characteristics curves.
Results: Among 222 18F-FDG PET/CT selected for 215 patients, 161 18F-FDG
PET/CT were performed in patients who presented inflammatory rheumatism as a final
diagnosis (of whom 57 PMR). The presence of at least three sites with significant uptake
identified PMR with a sensitivity of 86% and specificity of 85.5% (AUC 0.872, CI-95%
[0.81-0.93]). The mean FDG visual score cut-off to diagnose a PMR was 0.765 with a
sensitivity of 82.5% and specificity of 75.8% (AUC 0.854; CI-95% [0.80-0.91]). The mean
SUVmax cut-off to diagnose PMR was 2.168 with a sensitivity of 77.2 % and specificity of
3 Conclusions: This study suggest that 18F-FDG PET/CT had good performances to
4 Key words : PMR; 18F-FDG PET/CT; inflammatory rheumatism, uptake scores, SUVmax,
5 Abbreviations
ACR/EULAR: American College of Rheumatology / European League Against Rheumatism
ASAS: Assessment of Spondyloarthritis International Society
AUC: Area Under Curve
BASDAI: Bath Ankylosing Spondylitis Disease Activity Index
CRP: C-reactive protein
CT: Corticotherapy
DAS28-VS or DAS28-CRP: Disease Activity Score
EORA: Elderly-Onset Rheumatoid Arthritis
ESR: Erythrocyte sedimentation rate
18
F-FDG PET/CT: Fluorodeoxyglucose positron emission tomography coupled with computerized tomography
GCA: Giant cell arteritis
IR: Inflammatory rheumatism
LVV: Large vessel vasculitis
MBq/kg: Megabecquerel per kilogram body weight
PMR: Polymyalgia rheumatica
RA: Rheumatoid arthritis
ROC: Receiver Operating Characteristic
ROI: Region of interest
RS3PE: Remitting Symmetrical Seronegative Synovitis with Pitting Edema
SA: Spondyloarthritis
SAPHO: Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis
SUVmax: Maximum standardized uptake value
6
Introduction
Chronic inflammatory rheumatisms are common conditions among the general
population. Rheumatoid arthritis (RA) is the most frequent rheumatism in France, with a
prevalence of 0.35% (1). In people older than age 50, the prevalence of polymyalgia
rheumatica (PMR) and giant cell arteritis (GCA) are respectively 700/100 000 and 204/100
000 (2).
The ACR/EULAR’s 2010 criteria for RA (3) and its 2012 criteria for PMR (4) enable
orientation of the diagnosis of these diseases, however their sensitivities and specificities
remain limited (57.9% and 88.8% for RA, 66% and 81% for PMR respectively).
Moreover, the need to eliminate differential and associated diagnoses, such as neoplasias
and vasculitis (5,6) especially in elderly people, encourages additional examinations.
Fluorodeoxyglucose positron emission tomography coupled with computerized tomography
(18F-FDG PET/CT) in these cases seems useful. Macrophage activation and fibroblasts
proliferation enhanced by proinflammatory cytokines result in an increased
fluorodeoxyglucose (18F-FDG) uptake in articular, periarticular and vascular wall areas (7).
Inflammation targets the synovial membrane in patients suffering from RA. In cases of PMR,
it affects principally the serous bursa. Several studies demonstrated the usefulness of 18F-FDG
PET/CT in inflammatory rheumatism diseases (5,6,8–10) , especially PMR and in vasculitis.
18
F-FDG PET/CT enables a full-body map of vascular, articular and periarticular uptake
within a single examination (9,10).
Several scores have been developed for the diagnosis of vasculitis or inflammatory
rheumatism and to evaluate their activity (11–13) with relatively promising results.
The objective of our study was to evaluate composite periarticular scores derived from
18
7
Materials and methods
Patients
In this retrospective study, 478 patients were selected. Their 18F-FDG PET/CT were
performed between April 2011 and December 2015 and prescribed by the Rheumatology and
Internal Medicine Departments of our institution (Clermont-Ferrand, France).
18F-FDG PET/CT inclusion criteria were follow up of previously known rheumatic
diseases such as PMR, RA, GCA, spondyloarthritis (SA), diagnosis of suspected rheumatic
diseases and diagnosis of an unexplained biological inflammatory syndrome.
Following data were collected when available : indication of the 18F-FDG PET/CT (initial
test for inflammatory rheumatism or for an unexplained biological inflammatory syndrome,
test for treatment-resistance, screening for vasculitis or a neoplasia), rheumatism’s activity
parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR),
DAS28-VS or DAS28-CRP, treatment with corticosteroids or other immunosuppressants (including
duration and dose) and final diagnosis retained by rheumatologist or internal medicine
specialist according patient’s clinical and paraclinical data. 18
F-FDG PET/CT exams were not
included in the paraclinical tests used for the final rheumatic diagnosis. In majority, 18F-FDG
PET/CT were realized to rule out paraneoplastic rheumatism.
In case of an unclassified rheumatism, diagnosis was applied according to the 2010
ACR/EULAR’s criteria for RA (3), its 2012 criteria for PMR (4) and the 2009 ASAS’s criteria for SA (14). If the rheumatism did not meet these criteria, a final diagnosis was agreed upon
collegially by the three principal investigators. Some patients remained with a diagnosis of
8 Patients were sorted into 4 groups:
- The group named ‘inflammatory rheumatisms’ gathered patients with PMR, RA, SA,
GCA, microcrystalline rheumatism, synovitis-acne-pustulosis-hyperostosis-osteitis
(SAPHO), unclassified rheumatism, remitting seronegative symmetrical synovitis with
pitting edema (RS3PE), paraneoplastic rheumatism and psoriatic rheumatism.
- The group named “rheumatic diseases without inflammatory rheumatism” referred to
patients who ultimately presented discopathy, vertebral collapse, prosthetic loosening,
narrowing of the lumbar vertebral canal, tendinitis of the gluteus medius muscle,
fracture of the pelvis, shoulder-hand syndrome, fibromyalgia or osteoarthritis.
- The group named “infectious or inflammatory diseases” gathered a majority of
patients addressed for an unexplained biological inflammatory syndrome and who
ultimately displayed infectious or inflammatory diseases, some of them did not have
musculoskeletal manifestations.
- The group named “absence of inflammatory rheumatism” included patients in the
groups named “rheumatic diseases without inflammatory rheumatism” and “infectious or inflammatory diseases.”
80% out of GCA were proven histologically with a positive temporal biopsy. For the
others, the diagnosis was based on clinical and paraclinical data (imaging).
The patients provided their written informed consent to participate in this study.
The study has been approved by CECIC Rhône Alpes Auvergne, Grenoble, IRB 5921 on
12 November 2019 (IRB number: 5921).
18
F-FDG PET/CT imaging
After four hours of fasting, a minimal activity of 3MBq/Kg of 18F-FDG was injected into a
9 (Discovery ST or Discovery 710 Optima 660). In most cases, acquisition extended from the
skull to the upper third of the femurs, with the upper extremities situated either along the body
or above the head. Only 15% of the 18F-FDG PET/CT involved the entire body. 18F-FDG
PET/CT acquisitions were not contrast-enhanced.
Similar to Sondag et al. (9) method, 17 periarticular sites were analyzed using a visual
analysis to evaluate the intensity and the number of hotspots. A semi-quantitative analysis was
also realized for the 17 hotspots. These involved both shoulders, both acromioclavicular and
both sternoclavicular joints, the most intense interspinous bursa, both hips, both greater
trochanters, both ischial tuberosities, both iliopectineal bursa and both symphysis pubis
enthesis. Each uptake was sorted by visual analysis using a four-point scale from 0 to 3 in
comparison with liver uptake (0 : no uptake, 1 : uptake lower than the liver, 2: moderate
uptake, same as that of the liver, 3: uptake higher than the liver).
Two visual composite scores were therefore analyzed: the mean FDG uptake score at the
17 sites of an exam: F17 and the number of sites with significant uptake (score ≥ 2, cut-off proposed by Goerres et al. (15): Nb).
Moreover, the maximum standardized uptake value (SUVmax) was measured at the 17
hotspots for 222 18F-FDG PET/CT by a board certified nuclear medicine physician, blinded to
the clinical and paraclinical tests results, using Advantage Windows Server 3.2 (General
Electric Healthcare Systems, 2016). For determination of the SUVmax, a region of interest
(ROI) was manually placed over each of the 17 periarticular sites. Activity concentration
within the ROI was determined and expressed as SUV, where SUV is the ratio of the activity
in the tissue to the decay corrected activity injected into the patient and normalized for patient
10 considering the uptake given by the maximum pixel value within a region of interest in each
of the 17 hotpsots.
For PMR, RA and all pathologies taken together, 18F-FDG PET/CT were sorted into two
groups (< 3 sites with significant uptake, ≥ 3 sites with significant uptake) in order to compare
the rheumatism’s activity parameters.
Statistical analysis
Parameters were calculated and then compared within the different groups (PMR, RA,
SA, GCA, all inflammatory rheumatisms taken together, “absence of inflammatory
rheumatism” and “rheumatic diseases without inflammatory rheumatism”) as follows: - mean FDG uptake score (F17) and standard deviation,
- number of sites with significant uptake (Nb) and standard deviation,
The means of the scores were compared using the Kruskal-Wallis test.
Some other parameters were calculated and compared between the PMR +/- GCA group
and other patients as follows using the Wilcoxon-Mann-Whitney test :
- mean SUVmax for each of the 17 hotspots,
- mean SUVmax for the 17 hotspots.
The sensitivity and specificity for the diagnosis of PMR were calculated using ROC
curve.
Rheumatism’s activity parameters (CRP, duration and dose of corticotherapy, DAS28-VS
or DAS28-CRP) as well as age were calculated and compared based on the presence or
absence of three sites with significant uptake for the groups PMR, RA and all pathologies
taken together. The latter were compared using Student’s test or the Kruskal-Wallis test. A
11
Results Patients
Overall, 222 18F-FDG PET/CT were selected for 215 patients as part of the testing for
rheumatic diseases, vasculitis, neoplasias or the exploration of an unexplained biological
inflammatory syndrome. Flowchart is displayed in Fig. 1.
Distribution of 18F-FDG PET/CT according to the final diagnosis and characteristics of
the population are given in Table 1 and 2. Table 2 summarizes the characteristics of the
patients of the PMR group: median age 74.8 years (IQR 15.2), 31 women, 26 men, CRP 32
mg/l (IQR 66), 13 mg/day (IQR 5.8) corticosteroids. CRP values and corticosteroids dose
were respectively available for 53 and 30 patients of the PMR group. In our whole population,
these values were used respectively for 90 and 57 patients.
18
F-FDG PET/CT visual analysis
A visual score was calculated for 17 periarticular sites based on liver uptake comparison.
Summarized in Table 3, the mean FDG uptake score at the 17 sites (F17)was significantly higher in the group of PMRs compared with the group “absence of inflammatory rheumatism,” respectively, 1.32 ± 0.61 and 0.44 ± 0.31 (p < 10-7
). Likewise, the number of
sites with significant uptake (Nb) was also higher, respectively, 6.9 ± 4.88 and 0.62 ± 1.2 (p <
10-7), Table 3.
For the PMR diagnosis, the predictive cut-off values of the mean FDG uptake score (F17)
and the number of sites with significant uptake were determined respectively at 0.765
(sensitivity of 82.5%, specificity of 75.8%, AUC 0.854; CI-95% [0.80-0.91]) and greater than
or equal to three (sensitivity of 86% and specificity of 85.5%, AUC 0.872, CI-95%
12 Impairment of at least three sites (Nb ≥ 3) and a mean FDG uptake score greater than
0.765 (F17 > 0.765) appeared to be the most specific criteria (respectively 85.5% and 75.8%)
for identifying PMR.
For example, this maximum-intensity projection and the axial fused 18F-FDG PET/CT show a patient suffering from PMR with uptake at the 17 sites in figure 2.
Relationship between visual FDG uptake and rheumatism activity
Rheumatism activity parameters were calculated and compared in some groups according to the number of sites with visual uptake equal or superior to the liver background, which was
the most sensitive and the more specific score. Results are shown in Table 4.
CRP values of RA and “all pathologies taken together” groups were significantly higher in
patients who had at least three sites with significant uptake on their exams (respectively p =
0.0065 and p < 10-5). Likewise, DAS 28 in RA group was significantly higher (6.0 ± 1.3
versus 4.1 ± 1.3 with p = 0.0045).
Patients belonging to the group “all pathologies taken together” were older when there
were at least three sites with significant uptake on 18F-FDG PET/CT (p = 0.034).
Finally, we did not find any significant link between the dose or duration of corticosteroid
13
18
F-FDG PET/CT semi-quantitative analysis
SUVmax was measured on each of the 17 periarticular sites, Table 5. The mean SUVmax
at the 17 sites was significantly higher in the PMR +/- GCA group compared with the others,
respectively, 2.68 (±0.63) and 1.81 (±0.69) (p < 10-6).
The predictive cut-off of the mean SUVmax at the 17 sites for PMR was calculated at
2.168 (sensitivity of 77.2%, specificity of 77.6%, AUC 0.842; CI-95% [0.79-0.89]), Fig. 3.
Moreover, these results were also significantly higher in each of the 17 sites for the PMR
+/- Horton group.
The best predictive mean SUVmax cut-off to diagnose a PMR was determined at 2.168
(sensitivity of 77.2%, specificity of 77.6%, AUC 0.842; CI-95% [0.79-0.89]).
18
F-FDG PET/CT visual and semi-quantitative analysis
The sensitivities and specificities of four composite scores (F17 > 0.53, F17 > 0.765, Nb ≥
14
Discussion
Key findings of the study and comparison to the literature
To date, our study, with 222 18F-FDG PET/CT analyzed, has been one of the largest in
terms of evaluating 18F-FDG PET/CT in cases of inflammatory rheumatism. Visual and
semi-quantitative analysis were realized on 17 periarticular sites. Also, our work consolidates
various rheumatic diseases beyond cases of PMR, as was also done by Yamashita et al. (11),
who included cases of PMR, RA and SA. Yamashita et al. (11) demonstrated the usefulness of
scores when categorizing cases of PMR from other rheumatic diseases (particularly RA and
SA), by analyzing uptake in ischial tuberosities, in greater trochanters and in interspinous
bursa. Compared with the SA group, the ratio of FDG uptake was significantly higher in
patients with PMR and lower in patients with RA in ischial tuberosities (63.2, 93.8, and
12.5%, respectively; P < 0.001), greater trochanters (47.4, 81.3, 12.5%; P < 0.001), and
interspinous bursa (52.63, 75.0, and 12.50%; P = 0.001). Likewise, in our study, the number
of sites with significant uptake (Nb) was also higher in the PMR group compared to RA or
SA, respectively, 6.9 ± 4.88, 1.53 ± 2.18 and 2.56 ± 4.34, (p < 10-7), Table 3.
Wakura et al. (12) used uptake scores in nine articular and periarticular sites
(scapulohumeral and coxofemoral joints, greater trochanters, ischial tuberosities, interspinous
bursa at the cervical, thoracic and lumbar levels, entheses of the pectineal muscle and the
right femoral muscle) within two groups, PMR (15 patients) and EORA (7 patients). The
uptake scores allowed differentiation between the cases of PMR and EORA, with the PMR
group showing statistically significant higher scores. They also compared the SUVmax for
abnormal FDG accumulation sites between the PMR and EORA patients and observed no
significant differences between the two groups. Takahashi et al. (13) compared five articular
sites uptake between PMR and EORA patients. They found a sensitivity of 92.6% and a
15 uptake greater than that of the liver in the shoulders, interspinous bursa, iliopectineal bursa
and ischial tuberosities associated with the absence of uptake in the wrists. In the PMR group,
the results were statistically higher in the ischial tuberosities and interspinous bursa; however,
the uptake was lower in the wrists.Concerning our study, the number of sites with significant
uptake was higher in PMR patients than in the RA group respectively 6.90 ± 4.88 and 1.53 ±
2.18 (p < 10-7).
In order to diagnose PMR, our study found sensitivity and specificity values, respectively,
of 86% and 85.5 % when the 18F-FDG PET/CT presented at least three sites with significant uptake (Nb ≥ 3) which is higher to the results found by Sondag et al. (9) with a sensitivity of 74% and a specificity of 79% for a score Nb ≥ 3.
We found a significant link between the visual uptake intensity, an elevated CRP and
older age in the “all pathologies taken together” group when the 18
F-FDG PET/CT found at
least three sites with significant uptake (p ≤ 0.01). Sondag et al. (9), Moosig et al. (16) and
Okamura et al. (17) also found that CRP rates were correlated to the uptake intensity in
patients with PMR or vasculitis. We found a correlation between the intensity and number of
periarticular uptake (at least three sites with significant uptake) and a higher DAS 28 score in
patients with RA (6.0 ± 1.3 versus 4.1 ± 1.3 with p at 0.0045), which was also described by
Okamura et al. [15]. On the other hand, we did not highlight any significant link among the
presence of at least three sites with significant uptake, the dose and duration of
corticosteroids in the PMR and RA groups. This may be explained by the fact that in our
study, the rheumatism’s activity parameters had not been noted on the day of the 18
F-FDG
PET/CT. However, Blockmans et al. found a decreased uptake in the joints of the axial
skeleton after three months of corticosteroids in 35 patients suffering from PMR (18) and in
16 Blockmans et al. (18) did not recommend performing a 18F-FDG PET/CT when following
up cases of PMR because the decreased uptake was correlated to biological results. A more
recent study evaluated the use of 18F-FDG PET/CT for the assessment of tocilizumab as
first-line treatment in PMR patients (20). FDG uptake and bioclinical parameters (physical
examination, CRP, ESR) after treatment were significantly decreased. However, the
correlation between SUVmax and the other bioclinical parameters was low. This result may
be explained by the low level of SUVmax variation compared to that of the other parameters.
SUVmax was significantly decreased in all regions except in the shoulders, sternoclavicular
joints and cervical interspinous bursa. This persistent FDG uptake should be explained by
joint remodelling during the few weeks after tocilizumab treatment. In our study, a large
majority of patients (158) were free from any corticotherapy or immunosuppressive
treatments at the time of 18F-FDG PET/CT acquisitions guaranteeing the absence of any
induced treatment modification of 18F-FDG accumulation in joint sites. For the others,
presence or absence of corticotherapy or immunosuppressive treatments were not clearly
recorded in data files.
Our study show that the visual score is more sensitive and more specific than the
semi-quantitative score (sensitivity of 86% and specificity of 85.5% when at least three sites had a
significant uptake and sensitivity of 77.2% and specificity of 77.6 % when the mean
SUVmax at the 17 sites was equal or greater than 2.168). Moreover, the visual score is easier
to use in daily practice.
Approximately 20% out of patients with apparently isolated PMR showed LVV on 18
F-FDG PET/CT (21). As PMR and GCA are frequently overlap, typical F-FDG joint uptake
patterns and vascular uptake should be reported using a standardized 0-to-3 grading system
(no uptake ⩽ mediastinum, low < liver, intermediate = liver, high > liver), (21–23) with grade 2 considered as possibly positive for active LVV and grade 3 positive for active LVV (23).
17 Moreover, Slart et al. highlighted that 18F-FDG PET/CT exhibited high diagnostic
performance for the detection of LVV and PMR and was able to evaluate the response to
treatment (17,23,24).
Limitations and strengths of the study
This study has a few limitations. One concerns missing data relating to the study’s
retrospective design. In this monocenter study, inclusion criteria were heterogeneous. Indeed,
patients with various rheumatic diseases such as PMR, RA, SA, psoriatic rheumatism and
microcrystalline rheumatism were included and 18F-FDG PET/CT were achieved either for
initial diagnosis (to search for vasculitis or neoplasia) or during the follow up (after
treatment-resistance). Moreover, acquisition methods were heterogeneous, performed on two
different PET/CT systems leading to quantitative differences. In addition, 18F-FDG PET/CT
were analyzed by the same observer, which creates doubts concerning its reproducibility,
which was not assessed in our study. However, the use of a four-point scale, according to four
intensity levels from 0 to 3, in comparison with liver uptake, and SUVmax values enable this
variability to be reduced. This visual method was already used in the Deauville score for
therapeutic evaluation of lymphomas (25).
The large number of patients included especially PMR ones and the visual and semi
quantitative assessments are part of the strengths of the study.
Integration into the current understanding and future direction of the research
The 18F-FDG PET/CT allows us to confirm and map periarticular inflammation.
Therefore, it is an exam to be prioritized in clinically contentious cases, especially
18 Infections, neoplasias and the different rheumatic diseases can reproduce the same
musculoskeletal symptoms. The importance of early diagnosis enables initiation of the proper
treatment and reduction of anatomical and functional sequels.
Therefore, it is important to refine the reading of 18F-FDG PET/CT by precisely
indicating the number and intensity of the periarticular uptake. This allows the clinician to be
guided toward a diagnosis when the clinical presentation is atypical, especially in cases of
rheumatism in the elderly and, therefore, to have an impact on therapeutic management.
19
Conclusion
The visual and semi-quantitative scores turned out to be effective in differentiating PMR
from another rheumatism with a sensitivity of 86% and a specificity of 85.5% when at least
three sites had a significant uptake and a sensitivity of 77.2 % and a specificity of 77.6 %
when the mean SUVmax at the 17 sites was equal or greater than 2.168.
20
Figures and tables references
Figure 1: Flowchart
Figure 2: 18F-FDG PET/CT maximum-intensity projection showing uptake at the 17 sites of
the skeleton in a patient suffering from polymyalgia rheumatica (A), axial fused 18F-FDG
PET/CT with typical uptake of polymyalgia rheumatica at the lumbar interspinous bursa (B),
at the iliopectineal bursa (C), and at the ischial bursa (D).
Figure 3: ROC curve analyzing 18F-FDG PET/CT performance for the diagnosis of
polymyalgia rheumatica according to the mean SUVmax at the 17 sites
Table 1: Distribution of 18F-FDG PET/CT according to the final diagnosis
Table 2: Characteristics of the population
Table 3: Results of the different visual composite scores (m±s1) according to the final
diagnosis
Table 4: Rheumatism activity parameters (m±s1) based on the number of sites with significant
uptake on 18F-FDG PET/CT for PMR, RA and all pathologies taken together
Table 5: Results of the mean SUVmax (m±s1) according to the final diagnosis
Table 6: Sensitivities (Se) and specificities (Sp) of the different composite scores (F17 > 0.53,
F17 > 0.765, Nb ≥ 3, SUVmax > 2.168) based on the final diagnosis (all inflammatory
rheumatisms taken together, PMR, RA, SA, absence of inflammatory rheumatism and
21 Figure 1
22 Figure 2
18
F-FDG PET/CT maximum-intensity projection showing uptake at the 17 sites of the skeleton in a patient suffering from polymyalgia rheumatica (A), axial fused 18F-FDG PET/CT with typical uptake of polymyalgia rheumatica at the lumbar interspinous bursa (B), at the iliopectineal bursa (C), and at the ischial bursa (D)
23 Figure 3
ROC curve analyzing 18F-FDG PET/CT performance for the diagnosis of polymyalgia rheumatica according to the mean SUVmax at the 17 sites
24 Table 1
Distribution of 18F-FDG PET/CT according to the final diagnosis
Final Diagnosis Number of 18F-FDG PET/CT %
PMR 57 25.7 Of which, PMR + GCA 10 4.5 GCA (without PMR) 10 4.5 RA 49 22.1 SA 18 8.1 Psoriatic rheumatism 5 2.2 SAPHO 3 1.4 RS3PE 4 1.8 Paraneoplastic rheumatism 4 1.8 Microcrystalline rheumatism 5 2.2 Unclassified rheumatism 6 2.7
Rheumatic diseases without inflammatory rheumatism
32 14.4
Infectious or inflammatory
diseases 29 13.1
Of which, patients without musculoskeletal
manifestations
16 7.2
25 Table 2
Characteristics of the population
Characteristics All patients PMR +/- GCA Gender, n (%) Men Women 89/215 (41.4) 126/215 (58.6) 26/57 (45.6) 31/57 (54.4) Age, median (IQR), years 70.4 (20.5) 74.8 (15.2) CRP, median (IQR), mg/l 16 (49.6) 32 (66) Steroids dose, median (IQR),
mg/day 10 (9) 13 (5.8)
26 Table 3
Results of the different visual composite scores (m±s1) according to the final diagnosis
Parameters All IRs2 taken together (n= 161) PMR3 +/- GCA (n=57) RA4 (n=49) SA5 (n=18) GCA6 without PMR (n=10) Absence of IR (n=61) Rheumatic diseases without IR (n=32) F177 0.88 ± 0.63 1.32 ± 0.61 0.65 ± 0.41 0.69 ± 0.67 0.32 ± 0.31 0.44 ± 0.31 0.45 ± 0.29 Nb8 3.52 ± 4.47 6.90 ± 4.88 1.53 ± 2.18 2.56 ± 4.34 0.3 ± 0.67 0.62 ± 1.20 0.62 ± 1.13 1
m±s: Mean and standard deviation 2
IR: Inflammatory rheumatism 3 PMR : Polymyalgia rheumatic 4 RA : Rheumatoid arthritis 5 SA : Spondyloarthritis 6
GCA : Giant cell arteritis 7
F17 is the mean FDG uptake score studied in the 17 sites
27 Table 4
Rheumatism activity parameters (m±s1) based on the number of sites with significant uptake on 18F-FDG PET/CT for PMR, RA and all pathologies taken together
Parameters All pathologies taken together RA2 PMR3 ± GCA4 PET Nb5≥3 (n=73) PET Nb<3 (n =149) P6 PET Nb≥3 (n=10) PET Nb<3 (n=39) p PET Nb≥3 (n=48) PET Nb<3 (n=9) p CRP7 (mg/L) 58.6 ± 60.9 29.9 ± 46 p < 10 -5 74.0 ± 49.1 32.9 ± 53.2 0.0065 53.4 ± 61.7 43.1 ± 55.9 0.54 CT8 duration (months) NA9 32.4 ± 78.8 35.4 ± 68.6 0.94 21.7 ± 53.1 6.7 ± 11.7 0.95 CT dose (mg/day) 2.9 ± 4.2 3.7 ± 5.7 0.9 5.9 ± 6.6 11.3 ± 10.0 0.18 Age (in years) 70.8 ± 12.2 64.4 ± 21.2 0.034 65.4 ± 14 64.8 ± 13.2 0.80 72.9 ± 10.9 76.7 ± 6.7 0.36 DAS2810 NA 6.0 ± 1.3 4.1 ± 1.3 0.0045 NA 1
m±s: Mean and standard deviation 2
RA : Rheumatoid arthritis 3
PMR : Polymyalgia rheumatica 4
GCA : Giant cell arteritis 5
Nb is the number of sites with significant uptake (≥ liver uptake) 6 p: Significance value p 7 CRP : C reactive protein 8 CT : Corticosteroids 9
NA: Not applicable 10
28 Table 5
Results of the mean SUVmax (m±s1) on 18F-FDG PET/CT according to the final diagnosis
Parameters All PET/CT except PMR2 +/- GCA3
(N=165)
PMR2 +/- GCA3 (N=57)
Mean SUVmax Mean SUVmax Right sternoclavicular 1.93 ± 0.83 2.61 ± 0.87 Left sternoclavicular 1.89 ± 0.82 2.56 ± 0.75 Right acromioclavicular 1.84 ± 0.82 2.56 ± 0.84 Left acromioclavicular 1.89 ± 0.94 2.51 ± 0.81 Right glenohumeral 2.15 ± 1.17 3.13 ± 1.09 Left glenohumeral 2.11 ± 1.12 2.96 ± 0.99 Interspinous bursa 1.95 ± 0.99 3.13 ± 1.44
Right iliopectineal bursa 1.57 ± 0.75 2.48 ± 0.8
Left iliopectineal bursa 1.68 ± 1 2.61 ± 1.12
Right hip 1.78 ± 0.87 2.61 ± 0.95
Left hip 1.93 ± 1.16 2.75 ± 1.11
Right symphysis pubis enthesis 1.53 ± 0.63 2.4 ± 0.67
Left symphysis pubis enthesis 1.54 ± 0.69 2.5 ± 0.73
Right greater trochanter 1.72 ± 0.82 2.52 ± 0.84
Left greater trochanter 1.68 ± 0.69 2.63 ± 1.08
Right ischial tuberosity 1.74 ± 0.94 2.78 ± 0.97
Left ischial tuberosity 1.76 ± 0.94 2.86 ± 1.07
17 hotspots 1.81 ± 0.69 2.68 ± 0.63
1
m±s: Mean and standard deviation 2
PMR : Polymyalgia rheumatic 3
29 Table 6
Sensitivities (Se) and specificities (Sp) of the different composite scores (F17 > 0.53, F17 > 0.765, Nb ≥ 3, SUVmax > 2.168) based on the final diagnosis (all inflammatory rheumatisms taken together, PMR, RA, SA, absence of inflammatory rheumatism and rheumatic diseases without inflammatory rheumatism)
Parameters % All IRs1 (n=161) PMR2 ± GCA3 (n=57) RA4 (n=49) SA5 (n=18) Absence of IR (n=61) Rheumatic diseases without IR (n=32) F176 > 0.53 Se 61.5 91.2 51 33.3 32.8 34.4 Sp 67.2 59.4 45.7 44.6 38.5 43.2 F17 > 0.765 Se 48.4 82.5 32.7 33.3 14.8 15.6 Sp 85.2 75.8 59 60.3 51.6 56.8 Nb7 ≥ 3 SUVmax8 ≥ 2.168 Se 42.9 86 20.4 27.8 6.6 6.2 Sp Se Sp 93.4 42.2 78.7 85.5 77.2 77.6 63.6 20.4 59 66.7 27.8 62.7 57.1 21.3 57.8 62.6 21.9 61.1 1
IR: Inflammatory rheumatism 2
PMR : Polymyalgia rheumatic 3
GCA : Giant cell arteritis 4
RA : Rheumatoid arthritis 5
SA : Spondyloarthritis 6
F17 is the mean FDG uptake score studied in the 17 sites 7
Nb is the number of sites with significant uptake (≥ liver uptake) 8
30
Disclosure
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Acknowledgments
We want to express our gratitude to all the members of our PET staff for their contribution in
performing this study.
Data availability statement
Datasets are available on request.
Key points
QUESTION : The objective of our study was to evaluate visual and semi-quantitative
periarticular scores derived from 18F-FDG PET/CT for the diagnosis of PMR among
rheumatic diseases.
PERTINENT FINDINGS :
This retrospective study showed that the presence of at least three sites with visual significant
uptake and a mean SUVmax at the 17 sites equal or greater than 2.168 had high sensitivities
and specificities for the diagnosis of PMR.
IMPLICATIONS FOR PATIENT CARE :
An accuracy 18F-FDG PET/CT periarticular analysis guide the clinician when the clinical
presentation is atypical, especially in cases of rheumatism in the elderly and, therefore, have
31
Authors contributions
MC and AF especially contributed to acquire data, LO and LD to conception and design, CB, BB and CV to revise the manuscript and approve the final content of the manuscript, IM and AC to interpret data, SM, OA, MS, CM, AK and FC to enhance the intellectual content.
32
Conflict of interest statement
We don’t have any personal, professional or financial relationships that could potentially be construed as a conflict of interest.
33
References
1. Fautrel B, Cukierman G, Joubert J-M, Laurendeau C, Gourmelen
J, Fagnani F. Characteristics and management of rheumatoid
arthritis in France: Analysis of a representative French national
claims database resulting in an estimated prevalence of 0.35%. Jt
Bone Spine (2016) 83:461–462. doi:10.1016/j.jbspin.2015.05.010
2. Crowson CS, Matteson EL. Contemporary prevalence estimates
for giant cell arteritis and polymyalgia rheumatica, 2015. Semin
Arthritis Rheum (2017) 47:253–256.
doi:10.1016/j.semarthrit.2017.04.001
3. Cornec D, Varache S, Morvan J, Devauchelle-Pensec V, Berthelot
J-M, Le Henaff-Bourhis C, Hoang S, Martin A, Chalès G,
Jousse-Joulin S, et al. Comparison of ACR 1987 and ACR/EULAR 2010
criteria for predicting a 10-year diagnosis of rheumatoid arthritis.
Jt Bone Spine (2012) 79:581–585.
doi:10.1016/j.jbspin.2012.01.015
4. Dasgupta B, Cimmino MA, Maradit-Kremers H, Schmidt WA,
Schirmer M, Salvarani C, Bachta A, Dejaco C, Duftner C, Jensen
HS, et al. 2012 provisional classification criteria for polymyalgia
rheumatica: a European League Against Rheumatism/American
College of Rheumatology collaborative initiative. Ann Rheum
Dis (2012) 71:484–492. doi:10.1136/annrheumdis-2011-200329
5. Dalkılıç E, Tufan AN, Hafızoğlu E, Hafızoğlu M, Tufan F, Oksuz
F, Pehlivan Y, Yurtkuran M. The process from symptom onset to
rheumatology clinic in polymyalgia rheumatica. Rheumatol Int
(2014) 34:1589–92. doi:10.1007/s00296-014-3034-y
6. Lavado-Pérez C, Martínez-Rodríguez I, Martínez-Amador N,
Banzo I, Quirce R, Jiménez-Bonilla J, De Arcocha-Torres M,
Bravo-Ferrer Z, Jiménez-Alonso M, López-Defilló JL, et al.
(18)F-FDG PET/CT for the detection of large vessel vasculitis in
patients with polymyalgia rheumatica. Rev Esp Med Nucl Imagen
Mol (2015) 34:275–81. doi:10.1016/j.remn.2015.05.011
7. Matsui T, Nakata N, Nagai S, Nakatani A, Takahashi M, Momose
T, Ohtomo K, Koyasu S. Inflammatory cytokines and hypoxia
34
contribute to 18F-FDG uptake by cells involved in pannus
formation in rheumatoid arthritis. J Nucl Med (2009) 50:920–6.
doi:10.2967/jnumed.108.060103
8. Yamashita H, Kubota K, Mimori A. Clinical value of whole-body
PET/CT in patients with active rheumatic diseases. Arthritis Res
Ther (2014) 16:423. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/25606590 [Accessed
March 4, 2018]
9. Sondag M, Guillot X, Verhoeven F, Blagosklonov O, Prati C,
Boulahdour H, Wendling D. Utility of 18F-fluoro-dexoxyglucose
positron emission tomography for the diagnosis of polymyalgia
rheumatica: a controlled study. Rheumatology (Oxford) (2016)
55:1452–7. doi:10.1093/rheumatology/kew202
10. Elzinga EH, van der Laken CJ, Comans EFI, Lammertsma AA,
Dijkmans BAC, Voskuyl AE. 2-Deoxy-2-[F-18]fluoro-D-glucose
joint uptake on positron emission tomography images:
rheumatoid arthritis versus osteoarthritis. Mol Imaging Biol
(2007) 9:357–60. doi:10.1007/s11307-007-0113-4
11. Yamashita H, Kubota K, Takahashi Y, Minamimoto R, Morooka
M, Kaneko H, Kano T, Mimori A. Similarities and differences in
fluorodeoxyglucose positron emission tomography/computed
tomography findings in spondyloarthropathy, polymyalgia
rheumatica and rheumatoid arthritis. Joint Bone Spine (2013)
80:171–7. doi:10.1016/j.jbspin.2012.04.006
12. Wakura D, Kotani T, Takeuchi T, Komori T, Yoshida S, Makino
S, Hanafusa T. Differentiation between Polymyalgia Rheumatica
(PMR) and Elderly-Onset Rheumatoid Arthritis Using
18F-Fluorodeoxyglucose Positron Emission Tomography/Computed
Tomography: Is Enthesitis a New Pathological Lesion in PMR?
PLoS One (2016) 11:e0158509.
doi:10.1371/journal.pone.0158509
13. Takahashi H, Yamashita H, Kubota K, Miyata Y, Okasaki M,
Morooka M, Takahashi Y, Kaneko H, Kano T, Mimori A.
Differences in fluorodeoxyglucose positron emission
35
tomography/computed tomography findings between elderly
onset rheumatoid arthritis and polymyalgia rheumatica. Mod
Rheumatol (2015) 25:546–51.
doi:10.3109/14397595.2014.978936
14. Rudwaleit M, Van Der Heijde D, Landewé R, Listing J, Akkoc N,
Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M,
et al. The development of Assessment of SpondyloArthritis
international Society classification criteria for axial
spondyloarthritis (part II): Validation and final selection. Ann
Rheum Dis (2009) doi:10.1136/ard.2009.108233
15. Goerres GW, Forster A, Uebelhart D, Seifert B, Treyer V, Michel
B, Von Schulthess GK, Kaim AH. F-18 FDG whole-body PET
for the assessment of disease activity in patients with rheumatoid
arthritis. Clin Nucl Med (2006)
doi:10.1097/01.rlu.0000222678.95218.42
16. Moosig F, Czech N, Mehl C, Henze E, Zeuner RA, Kneba M,
Schröder JO. Correlation between 18-fluorodeoxyglucose
accumulation in large vessels and serological markers of
inflammation in polymyalgia rheumatica: a quantitative PET
study. Ann Rheum Dis (2004) 63:870–3.
doi:10.1136/ard.2003.011692
17. Okamura K, Yonemoto Y, Arisaka Y, Takeuchi K, Kobayashi T,
Oriuchi N, Tsushima Y, Takagishi K. The assessment of biologic
treatment in patients with rheumatoid arthritis using
FDG-PET/CT. Rheumatology (2012) 51:1484–1491.
doi:10.1093/rheumatology/kes064
18. Blockmans D, De Ceuninck L, Vanderschueren S, Knockaert D,
Mortelmans L, Bobbaers H. Repetitive 18-fluorodeoxyglucose
positron emission tomography in isolated polymyalgia
rheumatica: a prospective study in 35 patients. Rheumatology
(Oxford) (2007) 46:672–7. doi:10.1093/rheumatology/kel376
19. Blockmans D, de Ceuninck L, Vanderschueren S, Knockaert D,
Mortelmans L, Bobbaers H. Repetitive 18F-fluorodeoxyglucose
positron emission tomography in giant cell arteritis: a prospective
36
